The effects of UVB on ORAI1 channel and the role of ORAI1 channel on the UVB-induced epidermal hyperplasia and upregulation of TSLP and COX-2

Abstract

Epidermal keratinocytes, components of the outermost skin layer, are always exposed to the ultraviolet (UV) light from the sun. UV radiation induces a number of adverse biological effects, including inflammation and cancer. UV irradiation activates numerous signaling pathways that alter transcription including keratinocyte proliferation via activation of epidermal growth factor receptor (EGFR) augments, inflammation, and carcinogenesis.

Calcium (Ca2+) signaling is a major second messenger essential to a variety of intracellular signaling pathways. ORAI1 and its sensor STIM1 are activated by endoplasmic reticulum (ER) stress and induce Ca2+ influx from the extracellular medium, which is named store-operated calcium entry (SOCE).

Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine belonging to the Th2 cytokine family which has a key role in the initiation and maintenance of allergic inflammatory diseases. Cyclooxygenase-2 (COX-2) increases production of PGE2 known to promote skin carcinogenesis.

At present, nothing is known about the functional role of ORAI1 channel for UV induced biological effects in the skin. In this paper we have shown that UVB induces the expression of ORAI1. In addition, using topical application of ORAI1 inhibitor, we have confirmed functional roles of ORAI1 in UVB-induced change such as epithelial proliferation, TSLP induction and cyclooxygenase 2 (COX-2) induction. Thus, this study revealed that ORAI1 is a central modulator of the UV response of the skin that regulates cell proliferation, inflammation and even carcinogenesis. ORAI1 may represent a new therapeutic target for negative effects of UVB.